Smart Nanogatekeepers for Tumor Theranostics

Abstract
Nanoparticulate drug delivery systems (nano-DDSs) are required to reliably arrive and persistently reside at the tumor site with minimal off-target side effects for clinical theranostics. However, due to the complicated environment and high interstitial pressure in tumor tissue, they can return to the bloodstream and cause secondary side effects in normal organs. Recently, a number of nanogatekeepers have been engineered via structure-transformable/stable strategies to overcome this undesirable dilemma. The emerging structure-transformable nanogatekeepers for tumor imaging and therapy are first overviewed here, particularly for nanogatekeepers undergoing structural transformation in tumor microenvironments, cell membranes, and organelles. Thereafter, intelligent structure-stable nanogatekeepers through reversible activation and artificial individualization receptors are overviewed. Finally, the ongoing challenges and prospects of nanogatekeepers for clinical translation are briefly discussed.